The Medicines Company is discontinuing its phase 3 CHAMPION clinical trial program of antiplatelet drug cangrelor in patients undergoing PCI after failing to prove clinical efficacy as a result of safety findings by the independent Interim Analysis Review Committee (IARC).
The IARC, after conferring with the Drug Safety Monitoring Board, reported to the company that the CHAMPION-PLATFORM trial would not meet the goal of demonstrating persuasive evidence of clinical effectiveness that could form the basis for regulatory approval. The placebo-controlled trial compared treatment with cangrelor (in combination with usual care) to usual care in patients who require PCI.
Cangrelor was exclusively licensed from the London-based AstraZeneca in December 2003.
Based on updated information, the IARC also reported to Medicines that the CHAMPION-PCI trial, a clinical trial comparing treatment with cangrelor to clopidogrel (600 mg loading dose) in patients who require PCI, showed no significant differences in measures of clinical effectiveness.
Safety findings for the program were consistent with those expected from short-term P2Y12 platelet inhibition and included an increase in minor bleeding among patients given cangrelor in comparison to placebo, but not in comparison to clopidogrel (Plavix from Bristol-Myers Squibb and Sanofi Aventis).
Based on the totality of these data, the IARC has recommended that enrollment in both trials be discontinued and that all remaining data should be collected and analyzed.
The Parsippany, N.J.-based company said it is in the process of notifying the investigators and regulatory agencies of the discontinuation of the CHAMPION program.
The IARC also recommended that Medicines should consider focusing on short-term use of cangrelor in settings where oral drugs cannot be used or when a short half-life is highly desirable. The company had begun studying cangrelor in such a setting. The trial, known as the BRIDGE study, aims to establish the dosage of cangrelor that achieves greater than or equal to 60 percent inhibition of platelet aggregation for five days. The company plans to enroll approximately 200 patients who discontinue clopidogrel in preparation for cardiac surgery. The aim is to show safe ‘bridging' of patients during the pre- and post-surgical period of risk.
"We are disappointed that the CHAMPION program has not provided sufficient evidence of the clinical effectiveness of cangrelor to warrant completion of these Phase 3 trials. We thank the Investigators and oversight committees for their work and we will follow their guidance. The trials are being discontinued; we plan to finalize data collection and analyses, and we expect that the data will be presented at a major cardiology meeting in due course. We will now move forward more quickly with our studies where cangrelor is tested to enable safe 'bridging' of patients undergoing surgery...The development of cangrelor will therefore continue," said Clive Meanwell, MD, PhD, CEO of Medicines.